I’m 42 and have been taking letrozole during my past four cycles to try to increase my chances of conceiving naturally. My prescription has increased each cycle due to my relatively low 21-day progesterone labs — this cycle I took 10 milligrams a day for days 2 through 5 of my cycle. On the last cycle and this one, I’ve started experiencing hot flashes, particularly at night. The night sweats that I’ve had this month have disrupted my sleep so much more than usual that I can’t imagine continuing the letrozole treatment, much less increasing my prescription to 12.5 mg next cycle. Is the letrozole essentially pushing me into untreated perimenopause? Apart from the obvious side effects that I am currently experiencing (night sweats, vaginal dryness, daily spotting, generally feeling crappy), am I also causing permanent damage to my bone density?
—Too Tired and Sweaty to Think of a Creative Sign-Off
I am sorry that you are dealing with infertility. It is emotionally challenging under the best of circumstances. When you add treatments, which nearly always work by manipulating your hormone levels, the side effects can be intense.
Letrozole belongs to a class of drugs called aromatase inhibitors. Aromatase is an enzyme critical to the making of estrogen. Letrozole is used off-label — that is, using a medication for a purpose for which it is not approved by the FDA — to help induce ovulation in women who are not ovulating regularly on their own.
By blocking the production of estrogen, letrozole keeps estrogen low. When estrogen levels are low before ovulation, the pituitary gland responds by releasing more follicle-stimulating hormone (FSH). The hope is that higher levels of FSH will lead to ovulation.
Low estrogen levels can result in a number of symptoms, including hot flushes, night sweats, and sleep disruption. Whether low estrogen levels are from perimenopause or from medications, the symptoms are often the same.
Different reproductive endocrinologists use different drug protocols. While I am not a reproductive endocrinologist, I have often seen my colleagues continue the same dose of letrozole during several cycles as long as it is resulting in ovulation, even if it doesn’t result in pregnancy.
If you are not sure about the outcome of your letrozole cycles, you should ask your reproductive endocrinologist about how well the letrozole is working and how they envision moving forward in your case. Be honest about your side effects during this conversation.
Women typically take letrozole for five days early in their menstrual cycle. Once letrozole is stopped, estrogen levels rise. This is a critical step to prepare the uterine lining for an embryo and a key detail in answering your question about how low estrogen levels while taking letrozole might affect your bone density.
There is no data regarding the risk of osteoporosis after letrozole use for ovulation induction. There are likely two reasons for this. First, letrozole was approved for preventing the recurrence of breast cancer by the FDA in 2001. Even if the first women to take letrozole for ovulation induction were in their early 40s in 2001, they are just now in their 60s. We would not expect them to develop osteoporosis much before this.
Second, because most protocols have women take letrozole for just a few days each cycle, estrogen is low for only a few days per cycle. During the rest of the menstrual cycle, levels of estrogen would be normal. Bones are slow to change, so these few days of low estrogen each month are not very likely to have an appreciable effect in the context of a woman’s entire reproductive lifespan.
Ultimately, you should consider sharing your current side effects from letrozole with your reproductive endocrinologist and discussing next steps. However, because letrozole is lowering your estrogen levels for only a few days each cycle, I would expect the risk of contributing to significant bone loss later to be small, although there is currently no published data regarding the long-term effects of letrozole on bone density.
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